Occupational andEnvironmentalMedicine 1995;52:28-32



# Cancers 

# related to exposure 

## to 

# arsenic at a 

## copper 

# smelter

Philip E 

### Enterline, Richard Day, GaryM 

### Marsh



### Abstract 

### Objective-This is an

### update ofan

### earlier studyon the 

### relationbetweenexposure to arsenic in air 

### and deaths from 

### respiratory cancer. The 

### purpose was to verify earlier 

### findings of a 

### supralinear dose response 

### relation and to 

### examine rela

### tions with 

### other cancers, 

### particularly those 

### reported in 

### studies on 

### drinking water. 

### Methods-An earlier study of 2802 men 

### who worked at a 

### copper smelter for a 

### year or more 

### during the 

### period 1940-64 

### andwho were 

### followedup for

### deaths dur

### ing the 

### period 1941-76 

### was 

### updated until 1986. Estimates 

### of exposure for the 

### period 1977-1984 were 

### added. Results 

### and conclusions-The additional follow up 

### confirms the earlier 

### finding that at 

### lowdoses the 

### increments in 

### death rates for 

### respiratory cancer for a 

### given increment in 

### dose are 

### greater than at 

### high doses. The 

### additional follow up also shows 

### significant increases 

### in cancer 

### of the 

### large intestine and 

### bone, 

### and SMRs >150 

### for cancer 

### of the 

### buccal cavity and 

### pharynx, rectal cancer, 

### and 

### kidney cancer. 

### There was a 

### positive relation between 

### exposure to 

### arsenic in 

### air and kidney 

### andbone 

### cancer, but none for the other 

### cancers, except 

### respiratory.

(OccupEnvironMed 1995;52:28-32)

Keywords: arsenic; cancer; dose-response

We 

### (PE, 

### GM) 

### previously reported on the 

### mortality 

### experience of 2802 men 

### who were 

### exposed to 

### arsenic at a 

### copper 

### smelter at 

### Tacoma, WA

### after a

### year ormore 

### ofemployment 

### during the 

### period 

### 1940-64.' 3 These 

### reports 

### showed an excess in 

### deaths 

### from res

### piratory cancer 

### during the 

### period 1941-76 with 

### the excess 

### related to 

### cumulative airborne exposure to 

### arsenic. In

### themostrecent 

### report, 

### the 

### respiratory cancer 

### dose-response curve at lower 

### exposures was 

### much 

### steeper than at 

### higher exposures so that the 

### dose-response

curve was 

### supralinear (concave 

### downward). This was true 

### for the relative as 

### well as 

### the absolute response, 

### and for follow up 

### that 

### started at 

### entry into 

### the 

### study, or 

### follow up 

### that started at the 

### end 

### of

### exposure.3 Thus, in the 

### population we 

### studied, the increments in 

### respiratory cancer 

### per unit 

### dose were 

### greater at 

### lowexposures than at

### high. This is a 

### report on 

### the results of an 

### additional 10 

### years 

### of follow up, 

### until 1986. The 

### purpose is to 

### verify our 

### previous 

### findings and to 

### explore an 

### additional 

### question, and that is 

### whether 

### inhaled arsenic is related to 

### internal

cancers as

### well as to 

### respiratory cancer. The 

### copper smelter where workers in this 

### study were 

### exposed to arsenic 

### started operations 

### in 1913 and at one 

### timewas 

### the

### largest in the United 

### States, 

### producing about 

### 10% of 

### the 

### refined copper in the 

### entire country. For 

### many 

### years it was 

### the source- 

### of all 

### ofFthe arsenic 

### commerciallyproduced in the 

### United States. Further 

### information about 

### this 

### smelter is 

### contained in an

### earlierpaper.

Methods For the 

### entire 

### cohort of 2802 men 

### who worked 

### for a 

### year or 

### more 

### during the 

### period 1940-64 

### it was 

### possible to 

### determine vital status at 

### the end of 1986 

### for 

### 98-5%. An 

### addi

### tional 522 

### deaths were 

### identified, which increased the 

### total from 1061 in the 

### last report to 

### 1583. 

### Of 1583 known

### deaths, death 

### certificates were 

### obtained 

### for 1530 or 96 

### 6%. The 

### additional 522 

### deaths were 

### traced 

### through the 

### United 

### States Social 

### Security Administration, the United States 

### National Death

### Index, and

### bypersonal

### phone contacts. 

### Death 

### certificates were 

### obtained from state 

### Health Departments and coded 

### by a nosolo

### gist to the 

### underlying cause 

### of death accord

### ing to 

### the revision of 

### international classification

### ofcauses 

### ofdeath in

### effect at the time 

### of death. For 

### malignant 

### neoplasms expected numbers ofdeaths were 

### based upon the 

### mortalityofthe

### population ofthe State 

### of 

### Washington.4 These are 

### available for the entire

### followup

### period 1941-86 

### for

### malignant neoplasms but 

### only from 1960 

### for other

causes 

### of 

### death. 

### Thus, for this 

### report follow up 

### for 

### non-malignant disease 

### only starts in 

### 1960 

### whereas followup 

### formalignant disease starts in 1941. In the 

### calculation of 

### expected deaths 

### only 

### mortality of white men was used as 

### all the 2802 workers in the 

### study were men 

### and 

### nearly all were 

### white. 

### Expected deaths were 

### also 

### calculated with death rates 

### for Pierce 

### County, the 

### county where the 

### smelter is 

### located.4 Results were 

### about the same as when 

### Washington state rates were 

### used. Because of 

### larger numbers 

### of deaths 

### and more 

### stable rates 

### onlyWashington state rates are 

### used in 

### this report. 

### Excesses and 

### deficits in 

### mortality

are 

### expressed as a 

### standardized

### mortalityratio 

### (SMR). This is 

### theratio ofthe observed to 

### the 

### expectednumber 

### ofdeaths

### multipliedby 100. Department of Biostatistics, Graduate School of Public Health, Universityof Pittsburgh, PA P E Enterline RDay GMMarsh Correspondence to: DrPhilip E Enterline, Department ofBiostatistics, Graduate School ofPublic Health, Universityof Pittsburgh, Pittsburgh, PA 15261, USA. Accepted 6 September 1994 2829

Cancersrelated to exposure to arsenic at a coppersmelter

Expected deaths are age-time 

### specific death

rates 

### ofwhite men for the state ofWashington multiplied 

### by person-years lived by the cohort 

### in 

### five year 

### age-time intervals. The 

### SMRs

were 

### calculated with the computer program 

## OCMAP.5 Exposure to arsenic was estimated 

### from departmental measurements of arsenic in air contained in company annual reports that 

### started 

### in 1938, 

### and measurements 

### of urinary arsenic identified by department and worker started in 1948. We combined 

### these data to allow an analysis of the relation between the concentrations 

### of arsenic 

### in air and various

cancers. Measurements 

### ofarsenic in air were 

### mostly confined to departments inwhich arsenic was thought to be a problem. Measurements 

### of urinary arsenic, on the other hand, were offered to all workers, and they represent all departments ofthe smelter. The conversion of data ofurinary arsenic to air arsenic was made by the 

### identification ofdepartments and years for which data from both air and urinary arsenic were 

### available and 

### by the determination of the mathematical relation between the

two. Although a total of 34 pairs of data were available, six pairs were deleted, one pair because the value of arsenic in air was based

on only one sample and the other five pairs because notations in the annual reports indicated that the measurements of arsenic in air

were not representative of normal working conditions. The remaining 28 pairs of data represented 11 of the 33 departments at the smelter. Average concentrations of arsenic in air

were weighted to reflect as closely as possible actual exposures of workers. Before 1971, data of arsenic in air came from spot samples and tape samples. As far as possible these

were weighted for hours per shift at the sam

### ple location, numbers 

### of men at 

### that location

per shift, and frequencyofoperation (for sam

### ples that reflected exposure 

### from a 

### particular operation). 

### Starting in 

### 1971, 

### data for arsenic in air were 

### based on 

### readings from personal 

### samples. These seem to be 

### representative 

### of personal exposure 

### forparticular 

### departments. From these data an exposure matrix 

### of arsenic in air was developed by 

### department 

### and year 

### from 1938 up to 

### the time the smelter closed in 1984. 

### Combined with 

### job histories for each worker cumulative exposure was calculated 

### and expressed as

### pg/m'/y. For years 

### before 1938 

### the exposure 

### data 

### for 1938 were used. Additional details on the method 

### used in estimations of exposure are contained in an earlier report.3

RESULTS FOR CANCER Table 1 shows 

### the mortality experienced 

### for selected malignant neoplasms in total 

### and 

### by time since 

### first exposure. 

### Overall, there were 

### significant excesses 

### for all malignant ne oplasms taken together, cancer of the 

### large intestine, cancer 

### of the respiratory system, and bone cancer. When there were <20 years 

### since first exposure the 

### only 

### significant excess is for respiratory cancer. For >20 years since first exposure SMRs are generally higher but those that are significant are the same as 

### for the total cohort. As well as the cancers that were 

### significantly in excess in 

### table 1 

### there are three 

### sites for which there were 10 or more 

### deaths and for which the SMRs were >150 but were not significant. For cancer of the 

### buccal 

### cavity and pharynx the SMR was 168-7 based on 12 deaths. For rectal cancer the SMR was 176-0 based on 15 deaths, and for kidney cancer there were 11 deaths and the SMRwas 163-5. Ten of the 11 deaths from kidney cancer occurred >20 years after 

### first exposure.

Table I Observed (0) andexpected 

### (E) deaths andSMRsforselected cancers

### byyears since

### firstexposure, Tacoma coppersmelter

Total Exposure <20y Exposure 

### >20y
Cancersite 0 E SMR 0 E SMR 0 E SMR
Allmalignantneoplasms: 395 276-06 143-1" 43 36-10 119-1 352 239-95 146-7 Buccalcavityandpharynx 12 7-12 168-7 2 1-14 175-8 10 5-98 167-3 Digestive organs andperitoneum: 95 79-08 120-1 11 10-94 100-6 84 68-14 123-3 Oesophagus 7 6-08 115-2 0 0-64

- 7 5-44 128-8 Stomach 18 16-43 109-6 2 2-79 71-8 16 13-64 117-3 Large intestine 38 23-48 161-8** 2 2-61 76-8 36 20-87 172-5 Rectum 15 8-52 176-0 4 1-33 299-9 11 7-19 153-0 Biliarypassages and liver 1 4-72 21-2 0 0-58

- 1 4-13 24-2 Pancreas 14 16-26 86-1 2 2-19 91-5 12 14-07 85-3 All otherdigestive 2 3-59 55-7 1 0-80 125-0 1 2-79 35-8 Respiratory system: 188 89-65 209-7** 17 9-66 176 0* 171 79-99 213-8 Larynx 3 3-17 94-7 0 0-42

- 3 2-75 109-2 Bronchus, trachea, lung 182 85-03 214-1** 17 9-04 188-1* 165 75-99 217-1 All otherrespiratory 3 1-46 205-4 0 0-20

- 3 1-26 238-1 Breast 0 0-46

- 0 

### 0-10

- 0 0-36

- Prostate 28 25-62 109-3 2 1-23 163-2 26 24-39 106-6 Testes andothermale genital organs 1 1-31 76-6 1 0-70 143-2 0 0-61 Kidney 11 6-73 163-5 1 1 04 95 9 10 5-69 175-9 Bladder and otherurinaryorgans 8 9-61 83-2 1 0-94 106-7 7 8-67 80-7 Malignantmelanoma ofskin 1 2-56 39-1 0 0-55

- 1 2-00 49 9 Eye 1 0-28 361-6 0 0-04

- 1 0-23 428-1 Central nervous system 5 8-15 61-4 0 1-98

- 5 6-16 81-1 Thyroid andotherendocrine glands 1 1-00 

### 99-9 0 0-24

- 1 0-76 131-7 Bone 5 1-10 455-6* 0 0-28

- 5 0-82 610-2 Alllynphatic,

### haeatopoieeic: 24 27-21 88-2 7 5-16 135-5 17 22-05 77-1 Lymphosarcorna andreticulosaroma 3 5-36 55-9 0 1-21

- 3 4-15 72-3 Hodgkin's disease 2 2-91 68-8 2 1-20 166-4 0 1-70 Leukemia and leukemia 9 11-28 79-8 2 2-04 97-8 7 9-24 75-8 All otherlymphopoietic tissue 10 7-66 130-5 3 0-70 426-8 7 6-96 100-6 Allothermalignant neoplasms 15 16-20 92-6 1 2-11 47-5 14 14-09 99-3
*P<0-05;**P<001.Table 2 Observed (0) andexpected (E) deaths andSMRSforrespiratory cancerbycumulative airborne arsenic anddate ofhire, Tacoma copper

smelter Cumulative Mean Totalcohort Hired<1940 Hired >1940 exposure exposure Person- (ag/rM y) (totalcohort) years 0 E SMR 0 E SMR 0 E SMR

<750 405 20 445 22 14-29 154-0 2 3 08 65-0 20 11-21 178 4* 750- 1305 19 III 30 17 10 175-5** 5 7-33 68-2 25 9-77 256-0** 2000- 2925 15 804 36 17 17 209-7** 22 8-93 246-2** 14 8 23 170-1 4000- 5708 13 747 36 17-00 211-7** 15 10 01 149-9 21 7 00 300-2** 8000- 12 334 10 934 39 15 48 252-0** 28 10 98 255-1** 11 4-50 244-4* 20 000- 28 336 4 114 20 7-04 284-0** 14 5-56 251-7** 6 1-48 405-5** 45000- 58957 761 5 1-58 315-7* 5 1-48 338-7* 0 0 11

*P < 0-05; **P<001.



### Table 2 shows 

### therelationbetween cumulative exposure to 

### arsenic in 

### air expressed as 

### ,ug/m3/y and cancer 

### of the 

### respiratory system 

### for the entire 

### cohort, for the cohort 

### hired before 1940, and for the cohort hired in 1940


### or 

### later. The reason 

### for this 

### stratification is 

### that for the cohort 

### hiredbefore 1940 

### onlythe person-years 

### accumulated from 1941 were 

### followedup 

### fordeaths, whereas 

### forthe cohort hired in 

### 1940 and laterall theperson-years, to the

### endofthe followupperiod, were 

### assessed. The stratification to some extent also 

### separatedworkers before 1940 with relativelyhigh exposure 

### andwithpoor

### respiratoryprotection 

### from workers with lower exposure, 

### but with better 

### exposure data and

### perhaps better

### respiratoryprotection. Table 2 

### shows the data that are plotted with

### dose ona logscale in

### fig 1. For the 

### entire 

### cohort the SMRs are almost 

### a straight line. When the 

### cohort was 

### separated into those 

### hired

### before 1940, and 1940 or later theplots
are more 

### irregular, but trends are 

### roughly similar 

### to 

### that for the entire cohort. Some of the 

### differences are 

### probably related to 

### the smaller numbers 

### upon which 

### the divided cohort is 

### based and it does not seem that the 

### combination 

### ofthe two 

### cohorts is 

### inappropriate 

### for

### determination ofthe 

### shape ofthedoseresponse relation between 

### arsenic and respiratorycancer. 

### When 

### absolute rather 

### than relative increments in 

### mortality are 

### calculated the plots 

### for the entire 

### cohort are 

### similar to those in

### fig 1. 

### If, for

### the entire 

### cohort, doseis

### plotted

500 r

2 400

en

it

c 300 (a

° 200

(D 100 ---- Hired 1940+

---- Hired <1940
All-,-A-lre on an 

### arithmetic scale rather than on a 

### logarithmic scale the 

### dose-response curve 

### is
concave 

### downward- like 

### the relation previ

### ouslyreported fortheyears 1941-76.3 

### For the 

### entire 

### cohort, the linear correlation 

### between log dose and 

### SMRs in 

### fig 1 

### is 

### highly significant 

### (P <0-001). The 

### fitted regression equation between dose and SMRs is a 

### power 

### function:
SMR = 100 + 10-5 

### (cumulative

### exposure) 1279 

### Compared with 

### the regression equation 

### reported for the years 1941-76 

### this new 

### equation, which includes 10 

### years 

### additional 

### follow up, 

### has 

### slightly more curvature than 

### the old

### equation and 

### strengthens the 

### evidence for 

### relatively large increments in 

### respiratory

cancer at 

### low exposures. 

### Figure 2 

### compares the 

### dose-response curve 

### for the 

### period 1941-86 with the 

### curve previously reported for the 

### period 1941-76. Note that the 

### horizontal scale is arithmetic. The power 

### function for follow up to 1986 

### is an 

### almost perfect fit.Table 3 

### shows the 

### relation 

### of the other
cancer 

### sites alreadydiscussedwith 

### cumulative exposure to arsenic in air. Here cancer 

### of the 

### large intestine has been combinedwith colon
cancer as 

### these are sometimes 

### confused 

### diagnostically and, moreover, 

### the 

### aetiology of these cancers 

### is likely to be the same. There does not seem to 

### be any relation 

### between cumulative exposure to arsenic 

### in air and 

### either 

### colorectal or 

### buccal cancer. 

### There is a 

### weakrelationforkidneyand

### bone cancers.

400

C 350 Cl) I, 300

o 250 0

c 200 

## C.

it z 150!

075 750 7 500 75 000 Cumulative airarsenic 

### (ig/rmn y) Figure I The SMRsforrespiratorycancerforcumulative airbornearsenic anddateofhire. Coppersmelterworkers from Tacoma 1941-86. Data areplottedat the means of exposure intervals. Cumulative airarsenic 

## (igg/m3 y) Figure 2 The SMRsforrespiratorycancerforcumulative airbornearsenic. Coppersmelterworkersfrom Tacoma 1941-76 and1941-86. Data areplottedat themeans of exposure intervals. Fittedlines arefromcorresponding powerfunctions. 30 Enterline, Day, Marsh

AllworKers I

------- I

, .1 I I I I

------- JrTable 3 Observed 

### (0) andexpected (E) deaths andSMRSforselected cancersbycumulative exposure to airbornearsenic, Tacoma coppersmelter

Cumulative Buccal Colorectal Kidney Bone exposure 

### (pg9/mY) 0 E SMR 0 E SMR o E SMR 0 E 

### SAtR

<750 2 

### 1*07 186-7 5 4 23 118-2 0 

### 1*03

- 0 0-17

- 750- 2 1 29 154-8 9 5 30 169-8 2 1-23 162-5 0 0-19

- 2000- 5 1-37 366-2 12 6-02 199-3 1 1-38 78-2 0 0 21

- 4000- 3 1-36 220 3 13 6-34 205 0 3 1-29 232 2 1 0.21 470-0 8000- 0 1-30

- 10 6-32 158 2 2 1-21 165 6 4 0 20 1969-8** 20 000- 0 0-60

- 3 3-07 97-7 3 0-56 538-0* 0 0 09

- 45 000- 0 0-13

- 1 0-70 137-0 0 0-13

- 0 002 *p<005; **P<0-01.

RESULTS FOR OTHER CAUSES OF DEATH



### Data on 

### non-malignant diseases (table 1)


### were 

### calculated 

### for the period 1960-86. As 

### already noted, expected deaths are 

### based on the mortality in 

### the state 

### of Washington for theyears 1960-86. Therewere a

### total 

### of 1234 deaths for all causes 

### during these 

### years and the 

### SMR was 118-8 

### (P < 

### 0-01). When selected causes were 

### examined therewere sig

### nificant excesses for 

### ischemic heart disease (P < 

### 0-01) and for 

### non-malignant respiratory 

### disease, 

### excluding 

### bronchitis, emphysema, and asthma 

### (P < 0 

### 05). There were 428 

### deaths from ischemic 

### heart disease and the 

### SMR was 

### 115-0. 

### This was 

### weakly related to 

### cumulative exposure to 

### arsenic. For the 

### exposure 

### categories shown on 

### table 2, the 

### SMRs andnumberofdeaths were: 107-6 

### (55), 103-2 

### (67), 106-6 (74), 121-6 

### (87), 127-5 (91; P < 0 

### 05), 131-7 

### (46), and 89-5 

### (8). For non

### malignant respiratory disease there were 41 

### deaths and a 

### slightnegative 

### relation, with 

### the 

### less exposedworkers 

### having the

### highest SMR.

COMPARISONS WITH OTHER STUDIES 

### An

### associationbetween exposure to 

### arsenic in air 

### and respiratory or 

### lung cancer has 

### been 

### reported 

### for several other 

### occupationally 

### exposed

### populations.i" Evidence for the kind 

### of dose-response relation reported here for respiratory cancer 

### has recently been sum

### marised and 

### commented upon 

### by HertzPicciotto and Smithwithdata 

### fromone 

### ofour

600

### F

-- 5007

- Ronnskar E

---- Anaconda

Cl) aI 400

- Tacoma

c In (D 40 CL

0 X 200

_

75 750 7 500 Cumulative airarsenic (pg/m Figure 3 The SMRsforrespiratory cancer (A andTacoma) andlungcancer (Ronnskar) for airborne arsenic. Tofacilitatepresentation the a exposure categoriesforRonnskarhave beencon Tacomaplots are asforfig 1. Anaconda andR
areplottedatthemidpointofexposure intervals upper intervals 30 000 and 57 000, whichwere inpart on theexposuredistributions in thedata Tacoma. 

### earlier 

### reports.36 There are 

### data from 

### two copper smelters that seem to 

### be 

### comparable with 

### our study. 

### Figure 3 

### shows the 

### doseresponse relation 

### reported for a 

### United 

### States copper smelter at 

### Anaconda, MT 

### and for a 

### copper smelter at Ronnskar, 

### Sweden along with data 

### from our 

### study.'4 '5 

### As in fig 1, 

### the horizontal scale is 

### logarithmic. 

### Only data reported by one 

### of the 

### investigators 

### of the Anaconda 

### smelter are 

### shown.'4 Other data for the 

### Anaconda smelter have been 

### reported 

### by Lee-Feldstein but the shape 

### of the 

### doseresponse curves is 

### similar to 

### that in fig 

### 2.'3 There are 

### also exposure 

### data for the Anaconda 

### smelter that have been 

### adjusted downward, and thus 

### higher 

### SMRs for each 

### exposure category can 

### be 

### calculated. '4 

### This 

### raises the 

### dose-response curve, 

### particularly at 

### higher 

### doses where it is nearly midway between 

### the Tacoma and the 

### Ronnskardata. The 

### dose-response curves 

### for the two 

### copper 

### smelters located in 

### the 

### United States are 

### similar. For the Swedish smelter the 

### response interms 

### oflungcancer

### ishigherat

### each

### level of exposure than 

### for the United 

### States smelters. The authors 

### of the report on the 

### Swedish smelter 

### thought that some 

### of the excess 

### in 

### lung cancer 

### might be due to 

### an excess in 

### smoking when 

### compared with 

### the 

### general population. A more recent 

### report shows that 

### smoking

### probablywas not a 

### factor in 

### the 

### high deathrate 

### from lung

### cancer.'7

Discussion Studies 

### of cancer related to arsenic in 

### drinking water 

### indicate increases in cancer 

### of the 

### lung, 

### bladder, kidney, skin, liver, and

### colon.'8 19 

### Gibb and Chen have 

### compared studies of sites with excessive cancer 

### between 

### arsenic inhalation 

### (like our 

### study) 

### and arsenic 

### inges

### tion, and have 

### concluded that there is some 

### agreement. 

### Our 

### study lends some 

### support 

### for a 

### relation between exposure to 

### arsenic in 

### airand

### kidney cancer

### but little 

### support forthe othercancers 

### except 

### lung cancer. 

### One 

### important difference between studies of 

### occupationally and 

### environmentally 75000 

### exposed cohorts is 

### that for most 

### of the envi- 

# ~'y) ronmentally exposed cohorts 

### exposure starts Inaconda 

### at birth, whereas for the 

### occupationally cumulative 

### exposed cohorts exposure of 

### interest starts 4pperthree ibined. much later in 

### life. In our 

### study the mean 

### age 

### otonskar at first 

### exposure was about 30 years. If 

### the

u 

### exceptfor 

### latent 

## period for some cancers 

### caused 

### by
eusedbased 

### from ingestion is very 

### long these 

### might be missed

in a 

### study of 

### occupationally exposed Cancersrelated toexposure toarsenic at a coppersmelter 31

IIEnterline, Day, Marsh


### populations. We looked forskin cancers in the smelter 

### population of Tacoma 

### and 

### found no 

### excess.2' These are 

### rarely fatal and could 

### only be found at

### work, not

### very

### longafter the onset of 

### exposure. Skin cancer 

### related to 

### arsenic in 

### drinking water 

### does not 

### usually appear until after the 

### age of 30 and the 

### incidence rises 

### rapidlywith 

### age.22 Thus, the 

### latent 

### period for 

### skin cancer and

### perhaps other cancers related to 

### ingestedarsenic couldbe

### very

### long, so

### per

### haps this is the reason 

### these were not seen in 

### the smelter worker 

### population of Tacoma. It 

### may also be 

### that, as 

### noted 

### by Bates et 

### al, in 

### comparison with 

### populations exposed to 

### arsenic in 

### drinking water 

### the exposure 

### of our 

### population, and 

### perhaps other 

### populations 

### exposed to 

### arsenic in

### air is 

### relativelylow.'9 One cancer 

### with an 

### apparently short latent 

### period in this 

### study is 

### respiratory cancer. 

### As table 1 

### shows, a 

### significant excess 

### (SMR = 203 

### 3) occurred in <20 

### years. The 

### SMR remained around 200 in 

### successive 10 

### year 

### periods and was 151-9 

### >,50 years 

### since first 

### exposure. We are not aware 

### of 

### published studies of

### otherworkers from copper smelters that report increments in 

### respiratory or 

### lung

cancer 

### by time from first 

### exposure. 

### Ott et al 

### reported no

### deaths from

### respiratorycancerin a 

### population occupationally exposed to insecti

### cides 

### containing arsenic <15 

### years 

### from first 

### exposure 

### (0 4 

### expected), but did report
excesses 

### for the 

### subsequent time since 

### first exposure 

### categories." In a 

### study by us 

### (PE, 

### GM) of workers at a 

### copper smelter at Salt 

### Lake 

### City, UT where there was 

### exposure to 

### arsenic the 

### SMR for 

### respiratory cancer <20 

### years since 

### first exposure was 170-0 

### (11 

### deaths) and >20 

### years 107-8 

### (39 deaths).'221 

### Perhaps a 

### short latent 

### period is somehow related to 

### thewayexposure occurs in 

### the 

### lung

as 

### inhaled arsenic seems to 

### be retained in the 

### lung for 

### long periods.24 On 

### the other 

### hand, 

### perhaps the 

### lung has a 

### particular susceptibil

### ity. One curious 

### finding in studies of arsenic in 

### drinking water 

### is a 

### dose related excess 

### in 

### mortality from 

### lung cancer-an excess sur

### passed onlyby an excess in 

### urinary cancer." We are not aware 

### of any other 

### ingested substance 

### that may cause 

### lung cancer. The 

### dose-response relation between 

### airborne arsenic and

### respiratory cancer 

### found in 

### this 

### study is unusual. As 

### noted in our earlier 

### report, this could be because 

### air measurements are not 

### good measures 

### of 

### biological dose.3 The 

### relation is not 

### likely to be 

### due to 

### confounding, but this needs 

### further 

### study. 

### Smoking can be an 

### important confounder in 

### respiratory cancer and data on the 

### histories of the 

### study population for 

### smoking are 

### being collected. These will 

### be modelled 

### along with other 

### covariates in a 

### future

### publication. The excess we 

### found in 

### bone cancer 

### has not, to our

### knowledge, been

### reported in 

### other studies. As arsenic 

### is stored in the

### bone, how

### ever, this maybe an 

### important 

### finding.2526 

### Of the five 

### deaths coded 

### by our 

### nosologist to bone 

### cancer, two were

### mandible, one

### hip, one 

### spine, and one 

### ribs. For 

### the 

### spine and ribs 

### information on 

### the death certificate 

### indicated 

### that these may not 

### have been the 

### primary sites. 

### If we 

### had recoded 

### these, however, it 

### would have invalidated our 

### comparison with the external control

### population.

This researchwas supported inpartbythe US Environmental ProtectionAgency. (AgreementNo CR811173.)

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